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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:MAP2K5-MYRFL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAP2K5-MYRFL
FusionPDB ID: 51220
FusionGDB2.0 ID: 51220
HgeneTgene
Gene symbol

MAP2K5

MYRFL

Gene ID

5607

196446

Gene namemitogen-activated protein kinase kinase 5myelin regulatory factor like
SynonymsHsT17454|MAPKK5|MEK5|PRKMK5C12orf15|C12orf28|bcm1377
Cytomap

15q23

12q15

Type of geneprotein-codingprotein-coding
Descriptiondual specificity mitogen-activated protein kinase kinase 5MAP kinase kinase 5MAP kinase kinase MEK5bMAPK/ERK kinase 5MAPKK 5MEK 5myelin regulatory factor-like protein
Modification date2020032720200322
UniProtAcc

Q13163

Main function of 5'-partner protein: FUNCTION: Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. {ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}.

Q96LU7

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000560591, ENST00000178640, 
ENST00000354498, ENST00000395476, 
ENST00000340972, 
ENST00000547771, 
ENST00000552032, ENST00000299350, 
ENST00000535034, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 10 X 9=90029 X 16 X 7=3248
# samples 1226
** MAII scorelog2(12/900*10)=-2.90689059560852
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(26/3248*10)=-3.64296810415672
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAP2K5 [Title/Abstract] AND MYRFL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAP2K5 [Title/Abstract] AND MYRFL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAP2K5(67893087)-MYRFL(70272808), # samples:2
Anticipated loss of major functional domain due to fusion event.MAP2K5-MYRFL seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP2K5-MYRFL seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP2K5-MYRFL seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP2K5-MYRFL seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr15:67893087/chr12:70272808)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across MAP2K5 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across MYRFL (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000178640MAP2K5chr1567893087+ENST00000552032MYRFLchr1270272808+3960117262737671046
ENST00000178640MAP2K5chr1567893087+ENST00000547771MYRFLchr1270272808+4298117262737311034
ENST00000395476MAP2K5chr1567893087+ENST00000552032MYRFLchr1270272808+3338550531451046
ENST00000395476MAP2K5chr1567893087+ENST00000547771MYRFLchr1270272808+3676550531091034
ENST00000354498MAP2K5chr1567893087+ENST00000552032MYRFLchr1270272808+340862015632151019
ENST00000354498MAP2K5chr1567893087+ENST00000547771MYRFLchr1270272808+374662015631791007

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000178640ENST00000552032MAP2K5chr1567893087+MYRFLchr1270272808+0.0007508580.99924916
ENST00000178640ENST00000547771MAP2K5chr1567893087+MYRFLchr1270272808+0.0002402270.99975973
ENST00000395476ENST00000552032MAP2K5chr1567893087+MYRFLchr1270272808+0.0003681420.9996319
ENST00000395476ENST00000547771MAP2K5chr1567893087+MYRFLchr1270272808+0.000106640.9998933
ENST00000354498ENST00000552032MAP2K5chr1567893087+MYRFLchr1270272808+0.000483920.9995161
ENST00000354498ENST00000547771MAP2K5chr1567893087+MYRFLchr1270272808+0.0001954340.99980456

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for MAP2K5-MYRFL

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAP2K5chr1567893087MYRFLchr12702728081172182DTLGHGNGGTVYKQRQLPDTPPYSAS
MAP2K5chr1567893087MYRFLchr1270272808550182DTLGHGNGGTVYKQRQLPDTPPYSAS
MAP2K5chr1567893087MYRFLchr1270272808620155DTLGHGNGGTVYKQRQLPDTPPYSAS

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Potential FusionNeoAntigen Information of MAP2K5-MYRFL in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
MAP2K5-MYRFL_67893087_70272808.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:01KQRQLPDTPPY0.99990.67911223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:25KQRQLPDTPPY0.99510.75951223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:03KQRQLPDTPPY0.89860.56331223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-C15:06GTVYKQRQL0.99290.7316817
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:04KQRQLPDTPPY0.99770.73521223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:05KQRQLPDTPPY0.92360.65191223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-C03:05TVYKQRQL0.99920.8774917
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:27KQRQLPDTPPY0.99990.70211223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:135KQRQLPDTPPY0.99990.71041223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:33KQRQLPDTPPY0.99990.67911223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:34KQRQLPDTPPY0.99990.67911223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:125KQRQLPDTPPY0.99990.67911223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:50KQRQLPDTPPY0.99990.75461223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:24KQRQLPDTPPY0.99970.72781223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:53KQRQLPDTPPY0.99970.6571223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:12KQRQLPDTPPY0.99930.65741223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:35KQRQLPDTPPY0.99730.67551223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:39KQRQLPDTPPY0.99540.63711223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:54KQRQLPDTPPY0.98540.6241223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B15:20KQRQLPDTPPY0.9270.7341223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B35:28KQRQLPDTPPY0.90350.75841223
MAP2K5-MYRFLchr1567893087chr12702728081172HLA-B48:02KQRQLPDTPPY0.68640.72991223

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Potential FusionNeoAntigen Information of MAP2K5-MYRFL in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of MAP2K5-MYRFL

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
6167NGGTVYKQRQLPDTMAP2K5MYRFLchr1567893087chr12702728081172

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAP2K5-MYRFL

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN6167NGGTVYKQRQLPDT-6.11479-7.15009
HLA-B14:023BVN6167NGGTVYKQRQLPDT-4.76706-4.88046
HLA-B52:013W396167NGGTVYKQRQLPDT-6.87405-6.98745
HLA-B52:013W396167NGGTVYKQRQLPDT-5.3619-6.3972
HLA-A11:014UQ26167NGGTVYKQRQLPDT-9.79836-9.91176
HLA-A24:025HGA6167NGGTVYKQRQLPDT-8.83847-8.95187
HLA-A24:025HGA6167NGGTVYKQRQLPDT-8.05027-9.08557
HLA-B44:053DX86167NGGTVYKQRQLPDT-7.51915-7.63255
HLA-B44:053DX86167NGGTVYKQRQLPDT-4.45384-5.48914
HLA-A02:016TDR6167NGGTVYKQRQLPDT-2.8902-3.9255

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Vaccine Design for the FusionNeoAntigens of MAP2K5-MYRFL

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
MAP2K5-MYRFLchr1567893087chr12702728081223KQRQLPDTPPYCAAGCAACGCCAGCTCCCAGACACCCCGCCCTA
MAP2K5-MYRFLchr1567893087chr1270272808817GTVYKQRQLAGGCACAGTCTACAAGCAACGCCAGCT
MAP2K5-MYRFLchr1567893087chr1270272808917TVYKQRQLCACAGTCTACAAGCAACGCCAGCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of MAP2K5-MYRFL

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
SARCMAP2K5-MYRFLchr1567893087ENST00000178640chr1270272808ENST00000547771TCGA-DX-A1L3-01A

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Potential target of CAR-T therapy development for MAP2K5-MYRFL

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneMYRFLchr15:67893087chr12:70272808ENST00000552032125628_6480911.0TransmembraneHelical

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to MAP2K5-MYRFL

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to MAP2K5-MYRFL

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource